Proton Beam Radiation for Wilms Tumor

Overseen By Matthew J Krasin, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: Prior radiation, Unfavorable histology, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

95 Participants Needed

Trial Summary

What is the purpose of this trial?

Participants are being asked to take part in this clinical trial, a type of research study, because the participants have a Wilms Tumor cancer. Primary Objectives To determine whether delivery of proton beam radiation to a conformal reduced target volume in the flank allows normal flank growth compared to the contralateral untreated side and non-irradiated patients. Secondary Objectives To deliver proton beam radiation to a conformal reduced target volume (partial kidney proton beam radiation therapy) in the affected kidney(s) for patients with Stage V (bilateral Wilms tumor) and specific involved surgical margins yielding no reduction in the high control rates seen with more traditional flank / whole kidney fields. Exploratory Objectives * Study the feasibility of sparing the residual kidney, spine and liver in patients requiring whole abdomen radiation therapy using either a proton beam treatment technique or intensity-modulated radiation therapy ( IMRT) photon based technique. * Study the feasibility of delivering whole lung radiation therapy with proton beams with the goals of sparing the developing breast tissue, heart structures, thyroid and liver. * Develop simultaneous xenografts and organoid models from the same starting material to study Wilms tumor biology and compare responses to chemotherapeutic agents. * Define the evolution of organ specific (kidney, liver, pancreas, etc.) abnormalities (laboratory studies) as an early marker of possible late end organ damage and their relationship to radiation. * Study and evaluate impact of proton therapy on the musculoskeletal system and physical performance and compare with photon therapy cases treated with classical treatment fields. * Assess CTC-AE and Pediatric Patient Reported Outcomes during radiation and in follow-up, correlating with disease, treatment and patient variables. * Correlate quantitative MRI values, including apparent diffusion coefficient (ADC) values, with histopathology findings post-surgery in children with (bilateral) Wilms. * Assess daily variations in proton range along each treatment beam using standard pre-treatment cone beam CT or on-treatment MR.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

What data supports the effectiveness of the treatment Proton Beam Radiation for Wilms Tumor?

Proton beam therapy (PBT) is considered a promising treatment for childhood cancers, including Wilms tumor, because it can target tumors more precisely and reduce radiation exposure to healthy tissues, potentially leading to fewer side effects. Studies suggest that PBT may be particularly beneficial for tumors in complex areas or those surrounded by sensitive tissues, which is often the case in pediatric cancers. ^{1 2 3 4 5}

Is proton beam therapy generally safe for humans?

Proton beam therapy (PBT) is considered safe and is often used for treating childhood cancers and tumors near sensitive areas. Studies suggest it may reduce the risk of secondary cancers compared to traditional X-ray therapy. ^{3 4 6 7 8}

How is Proton Beam Radiation different from other treatments for Wilms Tumor?

Proton Beam Radiation (PBT) is unique because it precisely targets tumors with minimal damage to surrounding healthy tissues, making it especially beneficial for treating childhood cancers like Wilms Tumor. This precision is due to the Bragg peak effect, where protons release most of their energy directly at the tumor site, reducing side effects compared to traditional radiation therapies. ^{3 4 9 10 11}

Research Team

Matthew J Krasin, MD

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

This trial is for patients with a newly diagnosed Wilms Tumor, who haven't had abdominal radiation before. It's open to those who've only had specific initial chemotherapy or surgery, and are within certain time frames post-surgery. Pregnant women can't participate, nor can those unwilling to consent or previously treated with radiation in the areas targeted by this study.

Inclusion Criteria

I have not had radiation therapy targeted at my abdomen.

I have followed the specific chemotherapy plan outlined for my condition and may switch based on my response.

I am a woman who can have children and have a negative pregnancy test.

Exclusion Criteria

I have had radiation therapy before but may need it again for this trial.

Inability or unwillingness to provide written informed consent

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants undergo 6-12 weeks of induction chemotherapy before surgical resection

6-12 weeks

Surgical Resection

Participants undergo surgical resection at diagnosis or after induction chemotherapy

1 week

Adjuvant Radiation Therapy

Participants receive adjuvant proton beam radiation therapy based on stage and surgical findings

4-6 weeks

Systemic Therapy

Systemic therapy delivered in a standard of care manner according to histology and stage

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Treatment Details

Interventions

• Proton Beam Radiation (PBRT)

Trial Overview The trial tests if proton beam radiation can be delivered more precisely to reduce side effects and allow normal growth of non-cancerous tissue compared to traditional methods. It also explores how well it spares healthy organs during whole abdomen therapy and assesses its impact on physical performance versus photon therapy.

Participant Groups

Group I: Stage V Adjuvant RT: Active Control 3 Interventions

Participants will undergo partial nephrectomy after 6-12 weeks of induction chemotherapy. Those with evidence of LN involvement, surgical margin involvement, local or diffuse spill, gross disease in the renal bed or peritoneal implants, will receive adjuvant PBRT

Group II: Favorable Histology Stage I & II and FH Stage III/IV Active Control 1 Intervention

Favorable Histology Stage I \& II and FH Stage III/IV Delayed Local Control with clear surgical margins and pathologically negative lymph nodes. Participants will undergo complete surgical resection at diagnosis or after 6-12 weeks of induction chemotherapy.

Group III: Stage III & IV Adjuvant RT and Stage V Active Control 3 Interventions

Participants will undergo surgical resection at diagnosis or after 6-12 weeks of induction chemotherapy. Those with evidence of LN involvement, surgical margin involvement, local or diffuse spill, gross disease in the renal bed or peritoneal implants, will receive adjuvant PBRT.

Proton Beam Radiation (PBRT) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Proton Therapy for:

• Wilms tumor
• Brain tumors
• Breast cancer
• Esophageal cancer
• Eye cancer
• Gynecological cancers
• Head and neck cancer
• Liver cancer
• Lung cancer
• Lymphoma
• Pancreatic cancer
• Prostate cancer
• Rectal cancer
• Sarcomas
• Spinal cord tumors

Approved in European Union as Proton Therapy for:

• Wilms tumor
• Brain tumors
• Breast cancer
• Esophageal cancer
• Eye cancer
• Gynecological cancers
• Head and neck cancer
• Liver cancer
• Lung cancer
• Lymphoma
• Pancreatic cancer
• Prostate cancer
• Rectal cancer
• Sarcomas
• Spinal cord tumors

Approved in Canada as Proton Therapy for:

• Wilms tumor
• Brain tumors
• Breast cancer
• Esophageal cancer
• Eye cancer
• Gynecological cancers
• Head and neck cancer
• Liver cancer
• Lung cancer
• Lymphoma
• Pancreatic cancer
• Prostate cancer
• Rectal cancer
• Sarcomas
• Spinal cord tumors

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Findings from Research

Proton beam therapy (PBT) shows potential advantages over traditional photon therapy in treating pediatric brain and solid tumors, particularly in reducing early and late side effects of radiation, although data on outcomes is still limited due to the small number of treated children.

As more treatment centers adopt PBT, there is a need to optimize overall cancer care and follow-up to ensure effective disease control and improve the quality of life for survivors, while also considering the long-term costs associated with radiation side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam therapy in pediatric oncology. Merchant, TE.[2022]

Proton therapy using pencil beam scanning (PBS) significantly reduces radiation exposure to critical organs at risk (OAR) in patients with Wilms tumor, with mean doses to the contralateral kidney, bowel, and liver being much lower compared to traditional photon therapy.

In a study of 11 patients, PBS resulted in a mean dose of only 52 cGy to the contralateral kidney compared to 135 cGy with photons, indicating a potential for improved long-term health outcomes due to reduced toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pencil beam scanning proton therapy for treatment of the retroperitoneum after nephrectomy for Wilms tumor: A dosimetric comparison study. Vogel, J., Lin, H., Both, S., et al.[2018]

Proton beam therapy (PBT) has been safely implemented for treating pediatric malignancies in a cohort of 47 patients under 25 years old, demonstrating its feasibility in a clinical setting on the Indian subcontinent.

The study found that while PBT is associated with some acute toxicities, such as dermatitis and hematologic toxicity, these effects were manageable, indicating that PBT can be a viable treatment option for young patients with specific tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary Experience of Treating Children and Young Adults With Image-Guided Proton Beam Therapy in India. Chilukuri, S., Burela, N., Uppuluri, R., et al.[2021]

Proton beam therapy (PBT) usage in the US increased from 0.4% in 2004 to 1.2% in 2018, particularly among patients with cancers recommended for PBT by the American Society of Radiation Oncology, indicating growing acceptance and application of this treatment.

While PBT use for prostate cancer temporarily decreased from 2011 to 2014, it rebounded by 2018, suggesting fluctuations in treatment preferences or insurance coverage that may influence patient access to this advanced therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Proton Beam Therapy Use Among Patients With Newly Diagnosed Cancer in the US, 2004-2018. Nogueira, LM., Jemal, A., Yabroff, KR., et al.[2022]

In a study involving 11 patients with rectal cancer, preoperative short-course pencil beam scanning proton therapy (PBS-PT) effectively reduced radiation exposure to normal tissues compared to traditional photon therapies (3DCRT and VMAT).

PBS-PT provided similar coverage of the clinical target volume while significantly lowering the radiation dose to critical organs like the small and large bowel, bladder, and femoral heads, suggesting a safer treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Implementation of Preoperative Short-Course Pencil Beam Scanning Proton Therapy for Patients With Rectal Cancer. Jeans, EB., Jethwa, KR., Harmsen, WS., et al.[2022]

Proton beam therapy (PBS) significantly reduces the risk of secondary malignancies (SM) compared to X-ray-based treatments like 3D conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT), as shown in a study involving treatment plans for 17 patients.

The study found that PBS offers better protection for critical organs, such as the lungs and breasts, leading to lower estimated SM rates, making it a preferable option for treating thymic malignancies, especially in young female patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secondary Malignancy Risk Following Proton vs. X-ray Radiotherapy of Thymic Epithelial Tumors: A Comparative Modeling Study of Thoracic Organ-Specific Cancer Risk. König, L., Hörner-Rieber, J., Forsthoefel, M., et al.[2022]

In a study of 192 prostate cancer patients treated with proton beam therapy (PBT) over a median follow-up of 1.7 years, only 5 patients experienced grade 3 toxicity, with no occurrences of grade 4 or 5 toxicity, indicating a high safety profile for this treatment.

Patient-reported outcomes showed stable urinary function post-treatment, while sexual health scores declined slightly at 1 year but did not worsen thereafter; bowel function scores also decreased but stabilized, suggesting manageable side effects associated with PBT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early toxicity and patient reported quality-of-life in patients receiving proton therapy for localized prostate cancer: a single institutional review of prospectively recorded outcomes. Lee, HJ., Macomber, MW., Spraker, MB., et al.[2019]

In a study of 68 patients with non-metastatic major salivary gland tumors treated with proton beam radiation therapy (PBRT), the 3-year locoregional control rate was an impressive 95.1%, indicating high effectiveness in managing the disease.

PBRT was well tolerated by patients, suggesting it is a safe treatment option for major salivary gland tumors, with overall survival rates reaching 96.1% over the same period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes and prognostic factors of major salivary gland tumors treated with proton beam radiation therapy. Zakeri, K., Wang, H., Kang, JJ., et al.[2022]

Proton beam therapy (PBT) is feasible for treating infants with central nervous system tumors, showing promising short-term outcomes with a 3-year overall survival rate of 76.5% among 51 infants studied.

However, the treatment is associated with significant logistical challenges and potential for higher-grade toxicities, including late effects like endocrinopathy and hearing loss, highlighting the need for careful monitoring and longer follow-up to assess long-term impacts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Proton Beam Therapy for Infants with Brain Tumours: Experiences from the Prospective KiProReg Registry Study. Jazmati, D., Steinmeier, T., Ahamd Khalil, D., et al.[2021]

Proton minibeam radiation therapy (pMBRT) shows promise for treating high-grade gliomas and meningiomas, potentially offering reduced side effects and improved tumor control compared to standard radiation methods, based on theoretical evaluations of treatment plans.

While pMBRT provides similar dose distributions for organs at risk and lower average doses for shallow organs, standard proton therapy plans demonstrated slightly better target homogeneity, indicating that further optimization of pMBRT is needed for clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First proton minibeam radiation therapy treatment plan evaluation. Lansonneur, P., Mammar, H., Nauraye, C., et al.[2021]

Proton minibeam radiation therapy (pMBRT) shows promise for treating brain, lung, and liver metastases, providing similar or better tumor coverage compared to stereotactic radiotherapy (SRT) while using fewer treatment fields.

pMBRT significantly reduces the dose to organs-at-risk and keeps normal tissue exposure below tolerance limits, suggesting a safer treatment option compared to conventional proton therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton minibeam radiation therapy for treating metastases: A treatment plan study. Ortiz, R., Belshi, R., De Marzi, L., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Proton beam therapy in pediatric oncology. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Pencil beam scanning proton therapy for treatment of the retroperitoneum after nephrectomy for Wilms tumor: A dosimetric comparison study. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Preliminary Experience of Treating Children and Young Adults With Image-Guided Proton Beam Therapy in India. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Assessment of Proton Beam Therapy Use Among Patients With Newly Diagnosed Cancer in the US, 2004-2018. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical Implementation of Preoperative Short-Course Pencil Beam Scanning Proton Therapy for Patients With Rectal Cancer. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Secondary Malignancy Risk Following Proton vs. X-ray Radiotherapy of Thymic Epithelial Tumors: A Comparative Modeling Study of Thoracic Organ-Specific Cancer Risk. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Early toxicity and patient reported quality-of-life in patients receiving proton therapy for localized prostate cancer: a single institutional review of prospectively recorded outcomes. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Outcomes and prognostic factors of major salivary gland tumors treated with proton beam radiation therapy. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Feasibility of Proton Beam Therapy for Infants with Brain Tumours: Experiences from the Prospective KiProReg Registry Study. [2021]

10. England pubmed.ncbi.nlm.nih.gov

First proton minibeam radiation therapy treatment plan evaluation. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Proton minibeam radiation therapy for treating metastases: A treatment plan study. [2023]